Influence of active ingredient of chrysanthemum Parthenolide on mitochondrial function of CNE2 cell of human nasopharyngeal carcinoma and caspase activity

Abstract

Background: Parthenolide(PN) is the pricipal component of sesquiterpene lactones contained in some aromatic herbs. Nasopharyngeal carcinoma(NPC) occurs worldwide is one of highest incidence malignant tumor in south China. It is essential that using the PN as the therapy of health preserving of traditional Chinese medicine to develop the modern rehabilitation for NPC. Objective: To study the effect of sesquiterpene lactones (SLs), the active ingredient of chrysanthemum, on the mitochondrial function of NPC cell and activating passage of caspase. Design: Randomized controlled trial was conducted in this study. Setting and participants: Completed by the Department of Preventive Medicine, College of Public Health, Sun Yat-Sen University with object of poorly differentiated CNE2 cell strain. Intervention: Parthenolide is given and the dose-reaction and time effect are observed. The cellular mitochondrial function is detected with MTT color reaction, cellular caspase-9 and -3 activity were measured with substrate fluorescence spectrum, the release of mitochondrial cytochromic C (CytC) and cleavage segment of caspase-3 proenzyme were detected with protein immunity blotting; and specific inhibitor was applied for the blocking passage experiment of cellular caspase. Main outcome measure: cellular mitochondrial function, cellular caspase-9 and caspase-3 activity, release of mitochondrial CytC and cleavage of caspase-3 proenzyme. Results: After acted by PN(1-100 μmol/L) for 12 hours and 24 hours, MTT color reaction inhibition rate grows obviously with the dose, indicating dose-dependence (Pearson ' s γ = 0.7322, 0.7703, P < 0.05), IC50 was 252.94 μmol/L and 49.63 μmol/L respectively; but without rising of caspase-9 and -3 activity, release of CytC and formation of caspase-3 proenzyme cleavage. Affected by PN and caspase inhibitor at same time, caspase-9 and -3 activity were apparently lower than that of control and single PN effect. (t = 9.146, 8.280, 27.325, 27.450, P > 0.05). Conclusion: PN may induce lowered function and depletion of mitochondrion, but does not affect the activating passage of caspase in CNE2 cell. It is related with inhibited proliferation of intervened tumor cell and toxic reaction. The fact may provide evidence for the chemoprevention and rehabilitation of NPC.